Cerebellum最新文献

Spontaneous cerebellar hemorrhage (SCH) patients have a low success rate in extubation, but there are currently no guidelines establishing specifically for SCH patients extubation. The study included 68 SCH patients who received mechanical ventilation for more than 24 h, with 39 cases (57.3%) resulting in successful extubation. The multivariate analysis identified four factors significantly associated with extubation success: patient age under 66 years, an Intracerebral Hemorrhage (ICH) score less than 4 points, the presence of tissue shift, and a Glasgow Coma Scale (GCS) score (excluding language) above 6 points at extubation. By simplifying the prediction model, we obtained the Spontaneous Cerebellar Hemorrhage Extubation Success scoring system (SCHES-SCORE). Within the scoring system, 2 points were allocated for a GCS score (excluding language) above 6 at extubation, 1 point each for age under 66 years and an ICH score below 4, while tissue shift was assigned a negative point. A score of Grade A (SCHES-SCORE = 3-4) was found to correlate with a 92.9% success rate for extubation. The area under the receiver operating characteristic curve was 0.923 (95% CI, 0.863 to 0.983). Notably, successful extubation was significantly linked to reduced durations of mechanical ventilation, intensive care unit (ICU) stay, and total hospital stay. In conclusion, the scoring system developed for assessing extubation outcomes in SCH patients has the potential to enhance the rate of successful extubation and overall patient outcomes.

We report the prenatal diagnosis of Poretti-Boltshauser Syndrome (PBS) in a 36-year-old primigravida woman. At 22 weeks and 6 days of gestation, fetal ultrasound revealed a normally shaped but hyperechogenic cerebellum with all supratentorial structures appearing normal. Differential diagnosis included cavernous hemangioma, capillary telangiectasia, and cerebellar hemorrhage. Subsequent fetal cerebral MRI showed diffuse bilateral cerebellar modifications, reduced cranio-caudal diameter of the vermis, and pathological elongation and thickening of the superior cerebellar peduncles indicative of the molar tooth sign. Amniocentesis and whole exome sequencing identified two heterozygous truncating variants in the LAMA1 gene: c.3099G > A (p.Trp1033Ter) and c.3699T > A (p.Tyr1233Ter), confirming PBS.) Following the diagnosis, the pregnancy was terminated at 23 weeks and 5 days. Post-mortem examination supported the MRI findings consistent with PBS. This case highlights the importance of integrating ultrasound, MRI, and genetic analysis for accurate prenatal diagnosis and emphasizes the molecular diversity associated with PBS, including the presence of molar tooth sign mimics and a novel c.3699T > A variant.

Recent functional MRI studies have implicated the cerebellum in working memory (WM) alongside the prefrontal cortex. Some findings indicate that the right cerebellum is activated during verbal tasks, while the left is engaged during visuospatial tasks, suggesting cerebellar lateralization in WM function. The cerebellum could be a potential target for non-invasive brain stimulation (NIBS) to enhance WM function in cognitive disorders. However, the comprehensive influence of cerebellar lateralization on different types of WM and the effect of stimulation over the unilateral or bilateral cerebellum remain uncertain. This study was to investigate the cerebellum's functional lateralization and its specific impact on various aspects of WM in a causal manner using unilateral or bilateral cerebellar continuous theta burst stimulation (cTBS), a form of inhibitroy NIBS. Twenty-four healthy participants underwent four sessions of cTBS targeting the left, right, or bilateral Crus I of the cerebellum, or a sham condition, in a controlled cross-over design. WM performance was assessed pre- and post-stimulation using neuropsychological tests, including the 3-back task, spatial WM task, and digit span task. Results indicated that cTBS over the bilateral and right cerebellum both led to a greater improvement in 3-back task performance compared to sham stimulation. Additionally, active cTBS over the bilateral cerebellum yielded better performance in the spatial WM task than sham stimulation. However, no significant differences were observed between stimulation conditions for the auditory digit span task. This study may provide novel causal evidence highlighting the specific involvement of the right and bilateral cerebellum in various types of WM. Specifically, the right cerebellum appears crucial for updating and tracking 3-back WM content, while spatial WM processes require the coordinated engagement of both cerebellar hemispheres.

Under stress, Purkinje cells (PCs) undergo a variety of reactive morphological changes. These can include swellings of neuronal processes. While axonal swellings, "torpedoes", have been well-studied, dendritic swellings (DS) have not been the centerpiece of study. Surprisingly little is known about their frequency or relationship to other morphological changes in degenerating PCs. Leveraging a large brain bank, we (1) examined the morphology of DS, (2) quantified DS, and (2) examined correlations between counts of DS versus 16 other PC morphological changes in a broad range of cerebellar degenerative disorders. There were 159 brains - 100 essential tremor (ET), 13 Friedreich's ataxia, and 46 spinocerebellar ataxia (SCA) (14 SCA1, 7 SCA2, 13 SCA3, 5 SCA6, 5 SCA7, and 2 SCA8). DS were a feature of PCs across all these disorders, with varying morphologies and changes elsewhere in the dendritic arbor. On Luxol fast blue/hematoxylin and eosin-stained sections, the median number of DS per PC ranged from 0.001 in ET to 0.025 in SCA8. Bielschowsky-stained sections yielded higher counts, from 0.003 in ET to 0.042 in SCA6. Torpedo counts exceeded DS counts by one order of magnitude. DS counts were more robustly correlated with torpedo counts than with counts for any of the other PC morphological changes. In summary, DS ranged in prevalence across cerebellar degenerative disorders, from 1/1,000 to 42/1,000 PCs. Across disorders of cerebellar degeneration, these swellings of the dendritic compartment were most robustly correlated with swellings of the axonal compartment, suggesting a similar type of cellular response to duress.

In the past few years, SARS-CoV-2 infection has substantially impacted public health. Alongside respiratory symptoms, some individuals have reported new neurological manifestations or a worsening of pre-existing neurological conditions. We previously documented two cases of essential tremor (ET) who experienced a deterioration in tremor following SARS-CoV-2 infection. However, the effects of SARS-CoV-2 on ET remain largely unexplored. This study aims to evaluate the impact of SARS-CoV-2 infection on a relatively broad sample of ET patients by retrospectively comparing their clinical and kinematic data collected before and after the exposure to SARS-CoV-2. We surveyed to evaluate the impact of SARS-CoV-2 infection on tremor features in ET. Subsequently, we retrospectively analysed clinical and kinematic data, including accelerometric recordings of postural and kinetic tremor. We included 36 ET patients (14 females with a mean age of 71.1 ± 10.6 years). Among the 25 patients who reported SARS-CoV-2 infection, 11 (44%) noted a subjective worsening of tremor. All patients reporting subjective tremor worsening also exhibited symptoms of long COVID, whereas the prevalence of these symptoms was lower (50%) in those without subjective exacerbation. The retrospective analysis of clinical data revealed a tremor deterioration in infected patients, which was not observed in non-infected patients. Finally, kinematic analysis revealed substantial stability of tremor features in both groups. The study highlighted a potential correlation between the SARS-CoV-2 infection and clinical worsening of ET. Long COVID contributes to a greater impact of tremor on the daily life of ET patients.

The recognition that there is an innate immune system of the brain, referred to as the neuroimmune system, that preforms many functions comparable to that of the peripheral immune system is a relatively new concept and much is yet to be learned. The main cellular components of the neuroimmune system are the glial cells of the brain, primarily microglia and astrocytes. These cell types preform many functions through secretion of signaling factors initially known as immune factors but referred to as neuroimmune factors when produced by cells of the brain. The immune functions of glial cells play critical roles in the healthy brain to maintain homeostasis that is essential for normal brain function, to establish cytoarchitecture of the brain during development, and, in pathological conditions, to minimize the detrimental effects of disease and injury and promote repair of brain structure and function. However, dysregulation of this system can occur resulting in actions that exacerbate or perpetuate the detrimental effects of disease or injury. The neuroimmune system extends throughout all brain regions, but attention to the cerebellar system has lagged that of other brain regions and information is limited on this topic. This article is meant to provide a brief introduction to the cellular and molecular components of the brain immune system, its functions, and what is known about its role in the cerebellum. The majority of this information comes from studies of animal models and pathological conditions, where upregulation of the system facilitates investigation of its actions.

The cerebellum, traditionally linked to voluntary motor coordination, is now recognized for its role in nonmotor functions, including cognitive and social behaviors. This expanded understanding is vital for identifying neurodevelopmental disorders such as autism spectrum disorder (ASD), where cerebellar abnormalities are common. Recent research has identified specific cerebellar circuits contributing to these diverse functions, revealing interconnected pathways that regulate both motor and social behaviors. The cerebellum communicates extensively with the cerebral cortex, thalamus, and limbic structures through converging and diverging pathways, integrating sensory and motor information to fine-tune outputs and influence higher-order functions. Mouse models have been instrumental in dissecting cerebellar functions, with studies using genetic and neuroanatomical techniques to manipulate specific circuits and observe behavioral outcomes. Disruptions in cerebellar pathways can lead to motor deficits and social impairments, mirroring human neurodevelopmental disorders. This review explores the anatomical and functional organization of cerebellar pathways in mice, their role in behavior, and the implications of cerebellar dysfunction in disorders such as ASD. Understanding these pathways enhances knowledge of cerebellar contributions to behavior and informs therapeutic strategies for cerebellar and neurodevelopmental disorders, emphasizing the integral role of the cerebellum in motor and social functions.

Post-traumatic stress disorder (PTSD) is a debilitating mental health condition characterized by recurrent re-experiencing of traumatic events. Despite increasing evidence suggesting that the cerebellum is involved in PTSD pathophysiology, it remains unclear whether this involvement is related to symptoms directly resulting from previous trauma exposure, such as involuntary re-experiencing of the traumatic events, or reflects a broader cerebellar engagement in negative affective states. In this study, we investigated the specific role of the cerebellum in PTSD by employing a script reactivation paradigm with personalized traumatic and sad autobiographical memories in 28 individuals diagnosed with chronic PTSD. Functional magnetic resonance imaging (fMRI) data were collected while participants listened to their own autobiographical narratives recounted by a third person. Activation in the right cerebellar lobule VI was uniquely associated with traumatic autobiographical recall and was parametrically modulated by the severity of re-experiencing symptoms. In contrast, cerebellar Crus II showed increased activation during both traumatic and sad autobiographical recall, suggesting a broader involvement in processing negative emotions. Our findings highlight the unique contribution of the right cerebellar lobule VI in the processing of traumatic autobiographical memories, potentially through its engagement in low-level representation of sensory and emotional aspects of traumatic events.

COVID-19-associated cerebellar ataxia has rarely been reported and its clinical characteristics remain understudied. This study aims to report patients with COVID-19-associated cerebellar ataxia from our institution. COVID-19-associated cerebellar ataxia was diagnosed based on the prodromal COVID-19 infection and the exclusion of other causes. This study provides a summary of the patients' clinical presentations, neuroimaging features, and the results of anti-cerebellar antibody examinations. Our study included 11 patients and 4 were male. The median onset age was 38 years. Five patients also demonstrated signs of encephalopathy. Brain magnetic resonance imaging (MRI) was either unremarkable (n = 6) or showed bilateral cerebellar lesions (n = 5), which were typically transient, although brain atrophy could be observed later in the disease course. Anti-Homer-3 and anti-Yo antibodies were each detected in one patient, respectively. All patients received immunotherapy and nine improved. Compared with the late-onset group, individuals who exhibited ataxia earlier following COVID-19 onset (interval<5 days) were significantly younger [median age 18 (15.5-31) vs. 53.5 (44-64.8) years, p = 0.009] and more likely to present with encephalopathy (5/5 vs. 0/6, p = 0.002).They also experienced more severe symptoms [median modified Rankin scale (mRS) score at zenith 5 (5-5) vs. 2 (1.75-2.75), p = 0.017] and had a less favorable prognosis [median mRS score at the last follow-up 4 (2-5) vs. 1 (0-1.25), p = 0.009]. COVID-19-associated cerebellar ataxia can appear with encephalopathy. Brain MRI may show transient bilateral cerebellar lesions and brain atrophy later. Patients who exhibited ataxia earlier following COVID-19 were younger, had more severe symptoms and poorer outcomes.

Bi-allelic pathogenic variants in GRID2 have been initially associated to an autosomal recessive form of spinocerebellar ataxia, namely SCAR18. Subsequently, few monoallelic cases have been described. Here we present a new subject harboring a novel de novo heterozygous GRID2 missense variant presenting with progressive ataxia together with cerebellar atrophy and, for the first time, alpha-fetoprotein (AFP) elevation. We retrospectively collected data of the patient followed at our clinic. Genetic analysis was performed through clinical exome sequencing with an in-house in-silico ataxia-related genes panel. Variant effect prediction was performed through in silico modeling. The patient had normal psychomotor development except for mild fine and gross motor impairment. In adolescence, he started presenting dysarthria and progressive ataxia. Blood tests showed significant AFP elevation. Brain MRI showed cerebellar atrophy mainly involving the vermis. The novel de novo heterozygous GRID2 (c.1954C>A; p.Leu652Ile) missense variant was disclosed. This variant is located within a highly conserved site with low tolerance to variation and it is predicted to cause protein structure destabilization. GRID2 expression appears to be influenced by other genes related with ataxia and AFP elevation, like ATM and APTX, suggesting a possible shared mechanism. This additional patient increases the scarce literature and genotypic spectrum of the GRID2-related ataxia and evidences a fairly homogeneous phenotype of ataxia with oculomotor abnormalities for the autosomal-dominant form. Alfa-fetoprotein elevation is a novel finding in this condition and this data must be confirmed in larger case-series to definitively state that GRID2-related ataxia can be included among ataxias with AFP increase.